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Innovative therapies for treatment of post-traumatic stress disorder

02.09.2009

Pioneering research to imprPioneering research to improve outcomes for post-traumatic stress disorder presented at Military Health Research Forum

New research on post-traumatic stress disorder (PTSD) is being presented this week at the Military Health Research Forum (MHRF), a scientific conference hosted by the Department of Defense (DOD) Congressionally Directed Medical Research Programs (CDMRP).

Depending on the conflict in which they served, 10 to 30 percent of soldiers who have spent time in war zones experience the debilitating and life-altering symptoms of post-traumatic stress disorder (PTSD). With the active duty service member and veteran populations growing, PTSD is on the rise and researchers are working to improve care provided to military personnel.

A number of PTSD-focused studies presented at the MHRF evaluate the effectiveness of both pharmacologic and alternative treatment options. Topics examined include employing virtual environments and novel medicines to help military personnel diagnosed with PTSD and/or other co-morbidities, and the use of psychiatric service dogs to help troops manage the symptoms of PTSD.

"PTSD is a condition that has affected decades of war veterans, and treatments continue to evolve," stated Captain E. Melissa Kaime, M.D., Director of the CDMRP. "The novel PTSD research being presented at the MHRF represents advancements in therapy for this condition that we believe will improve patient care and outcomes for our service men and women."

Virtual Environments for Cognitive and Affective Dysfunction in Mild Traumatic Brain Injury and Post-Traumatic Stress Disorder: Development of a 21st Century Treatment Platform

Principal Investigator: Charles Levy, M.D., North Florida Foundation for Research and Education, Inc.

About 20 percent of combat veterans returning from Iraq suffer from mild traumatic brain injury (mTBI) or PTSD. Treatment for these conditions consists of medication and traditional psychotherapy, demanding frequent travel to a clinic, a potential hardship for many veterans.

Researchers led by Charles Levy, M.D., chief of Physical Medicine and Rehabilitation Services for the North Florida/South Georgia Veterans Health System, seek to leverage combat veterans' comfort and familiarity with communications technology and immersive environments (through cell phones, the internet, and video games) and build a prototype of a virtual world environment (VWE) in which to conduct therapy. The VWE will simulate everyday life encounters that are challenging to those with mTBI/PTSD, and allow the veteran and therapist to confront and overcome barriers that block successful social reintegration.

The clinical team chose a supermarket as the virtual scenario where veterans could receive cognitive and emotional challenges, including following a shopping list, purchasing items, making change, colliding with other shopping carts, and engaging with clerks and other patrons at check-out. Currently, a virtual supermarket is under construction that allows a therapist and patient, each at their own computer, to enter the virtual supermarket and experience these challenges together.

This research explores an innovative new concept. Previous use of virtual reality exposure among combat veterans has been limited to portraying battle as a part of exposure therapy.

"Oftentimes, the nuances of everyday life can unexpectedly trigger angry responses from warfighters hindered by mTBI and PTSD," Levy said. "This project shows great potential to expedite and expand care to veterans and wounded warriors in a short timeframe, in a way that minimizes travel for treatment, and in a cost-effective manner."

The combination of PTSD and alcohol dependence is a serious clinical condition for military veterans. When a veteran suffers from PTSD and alcohol dependence simultaneously, he or she generally experiences more psychosocial and medical problems, more frequent relapses, and more serious symptoms than those who suffer from only one or the other. Research into the treatment of these disorders has included the use of medications, which has been proven effective in alcoholism, clinical depression, and, in some cases, for symptoms of PTSD in those without simultaneous alcoholism. Preliminary data from two clinical trials presented at the MHRF show that therapeutic options may be effective in treating both symptoms of PTSD and alcohol dependence.

In the first clinical trial, 93 veterans with PTSD and alcohol dependence, who were psychiatrically stable, were randomized to receive naltrexone (opioid antagonist) and disulfiram (Antabuse) alone or in combination for 12 weeks. Results showed that patients with PTSD experienced less alcohol craving, used less alcohol, and had fewer psychiatric symptoms when taking medication (either or both of the drugs), compared to those on placebo.

The second study compared paroxetine, the serotonin re-uptake inhibitor, with desipramine, the noradrenergic re-uptake inhibitor, in reducing the symptoms of PTSD and alcohol consumption in veterans with acute cases of PTSD (when symptoms have lasted less than three months) and alcohol dependence. The study also examined whether naltrexone further reduced alcohol consumption. Preliminary findings show that desipramine and paroxetine are equally effective in reducing symptoms of PTSD. However, there was no advantage to including naltrexone as a combination therapy to reduce alcohol consumption.

"Post-traumatic stress disorder coupled with alcohol dependence continues to handicap our veterans," says Principal Investigator Ismene Petrakis, Associate Professor of Psychiatry at the Yale University School of Medicine. "These studies suggest that there are treatments available for patients who are suffering acute symptoms as well as for those who are relatively stable."

Soldiers who experience traumatic nightmares and sleep disturbances have less than optimal functioning in the demanding combat environment, and these symptoms are difficult to treat. Prior research has revealed that prazosin improves sleep and daytime function in Vietnam combat veterans with chronic PTSD and is a highly effective and well-tolerated option for the reduction and possible elimination of trauma nightmares.

Based on this initial research, Murray A. Raskind, M.D., extended this investigational therapy to soldiers in the field. Raskind, director of the VA Northwest Network Mental Illness Research, Education and Clinical Center in Seattle, Washington, conducted the study with the assistance of Major Jess Calohan, an Advanced Registered Nurse Practitioner who was in charge of a combat stress control team in northern Iraq. In the study, 13 active duty soldiers received between 1 mg and 10 mg of prazosin at bedtime. All had experienced life-threatening combat events or other traumatic events.

The soldiers were evaluated at baseline and follow up using the Clinician-Administered PTSD Scale to evaluate changes in the "recurrent distressing dreams" and "disturbed sleep" items. In addition, the Clinical Global Impression of Change was used to evaluate change in daytime function and individual overall sense of well-being. Nine of the 13 soldiers (70 percent) showed marked or moderate improvement in daytime function and well-being. In addition, on a 0 to 8 scale (8 being the highest rating of trauma), the mean trauma nightmare score decreased from 7.8 to 2.9 (p

Addressing safety concerns, no soldier worsened on any parameter. The open-label trial results are consistent with placebo-controlled prazosin trials in chronic PTSD in Vietnam veterans and civilians. Because clinical trials are not permitted in a combat setting, this study's carefully quantified results of dosed open-label treatment may be the highest quality data currently obtainable.

"Withstanding the constant demands and challenges faced by troops during combat results in exhaustion and disturbed sleep," Raskind said. "Discovering effective treatment options that encourage sleep grants soldiers the ability to perform at full capacity when needed."

The Use of Psychiatric Service Dogs with Soldiers Who Have PTSD Principal Investigators: Craig Love, Ph.D., Westat, Inc., and Joan Esnayra, Psychiatric Service Dog Society

Psychiatric service dogs are trained to meet the disability-related needs of people living with a variety of psychological conditions, including PTSD. A preliminary survey of people using psychiatric service dogs indicates that 82 percent of those with a PTSD, diagnosis reported a reduction in symptoms after being partnered with a trained dog. Another 40 percent report that their use of medication decreased subsequent to a human-canine partnership. Many reported in hindsight that their dogs could sense oncoming episodes of mental illness, such as manic episodes and panic attacks, even before the patients themselves could perceive the change.

A partnership of the Psychiatric Service Dog Society, Westat, the National Institutes of Health, and Walter Reed Army Medical Center is testing the effectiveness of the psychiatric service dog intervention for soldiers and veterans who are disabled by PTSD as well as the feasibility of implementing a psychiatric service dog training program at a military medical facility.

Study participants, soldiers disabled by PTSD, will be randomly assigned to one of two groups over a 12-month period. One group of 10 soldiers will receive a dog and professional training, while another group of 10 will receive neither. Both groups will undergo the usual treatment protocol for soldiers with PTSD at Walter Reed Army Medical Center. Participants will be evaluated throughout the 12-month period to assess their symptom improvement and illness management.

"Dogs can be trained to know their companions' needs and respond to them in unique ways," said Craig Love, of Westat, Inc. a private research organization. "We hope to show that this human-canine partnership is effective from both a clinical and cost standpoint so more soldiers and veterans can take advantage of this type of therapy."

About the Military Health Research Forum

The MHRF is a scientific conference for presenting research studies funded by the DOD CDMRP Peer Reviewed Medical, Gulf War Illness, and Psychological Health and Traumatic Brain Injury Research Programs. Research supported by these programs addresses the healthcare needs of the Armed Forces and their families, veterans and the American public.

The MHRF brings together scientists, clinicians, consumer advocates, policymakers, and the military to learn about research and product development advancements supported by the host programs. The conference includes invited presentations by noted scientists, educational sessions on topics of general interest and poster and symposium presentations by CDMRP-funded investigators across programs.The MHRF is designed to promote the exchange of ideas to facilitate research progress, the development of new partnerships and the translation of research findings into field-ready methods and products.

About the Congressionally Directed Medical Research Programs

In the early 1990s, the breast cancer advocacy community launched a grassroots effort to raise public awareness of the crucial need for increased funding of breast cancer research. Beginning in fiscal year 1992 (FY92), Congress appropriated $25 million for breast cancer research to be managed by the DOD. The following year, Congress continued to respond to the advocacy movement and appropriated $210 million for breast cancer research, marking the beginning of the U.S. Army Medical Research and Materiel Command's CDMRP. The CDMRP represents a unique partnership among the public, Congress and the military. Because of continued and expanded advocacy efforts, the CDMRP has grown to encompass multiple targeted programs and has received more than $5.3 billion in appropriations from its inception in FY93 through FY09.

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